for Zolgensma, which isn’t just the second gene therapy ever to get to market in the US, following the approval of Luxturna, from Spark Therapeutics, in 2018. It is the first to go head to head with an established medicine. There is no commercial competition for the only other FDA-approved gene therapy, Luxturna, which treats an inherited form of vision loss.
“This will be a very important launch to track—both for Biogen as well as Novartis,” Raffat wrote.
In SMA, a genetic mutation causes the lack of a key protein, SMN, which in turn leads to the death of motor neurons. The prognosis for Type 1 SMA, diagnosed in infants, is particularly grim. Kids who inherit the disease could die by the age of 2. More moderate forms rob people of their ability to walk and function independently. Many SMA patients of all types have trouble breathing, sucking, and swallowing because of muscle weakness; the more severe cases make patients vulnerable to dangerous respiratory complications, like lung infections. The disease affects an estimated 10,000 to 25,000 people in the US, according to the nonprofit SMA Foundation.
Until the FDA approved Spinraza in 2016, there were no therapeutic options for SMA, a progressive genetic disease. But Spinraza has shown it can change the trajectory of SMA, particularly when given to patients early enough. An experimental oral liquid solution from Roche, risdiplam, has also shown promise in early tests. Both are meant to be chronic treatments; Zolgensma is different. It’s a one-time treatment that uses a modified virus to deliver instructions into the body to produce a missing protein, SMN, hopefully for life.
In clinical testing, Type 1 patients taking Zolgensma hit developmental milestones they typically wouldn’t—sitting up, rolling over, walking, and more. In some cases, the effects have lasted as long as four years. Promising signs have been seen in others as well. (The program was originally discovered at Nationwide Children’s Hospital in Columbus, OH. As Xconomy recently reported, Zolgensma played a key role in Nationwide’s ambitions rise to become an important gene therapy center.)
Biopharma companies have been pouring money into gene therapy through a spate of deals, convinced of its promise. But so far, the few products to reach the market have struggled commercially. Glybera, the first approved gene therapy in the Western world, was yanked from the market. The second, Strimvelis, disappointed; GlaxoSmithKline sold it to Orchard Therapeutics in 2018. Luxturna generated $27 million in its first year, but the treatment is for an ultra-rare condition. Zolgensma will be gene therapy’s biggest test case to date.
Worries about the effect of the therapy wearing off aren’t the only uncertainties.
While Zolgensma hasn’t yet led to big safety problems, Novartis just recently said it would review whether a patient’s death in a European trial was related to the gene therapy. The shadow of a gene therapy trial death two decades ago still looms over the industry. Teenager Jesse Gelsinger died in a clinical trial at the University of Pennsylvania in 1999, bringing work in the budding field to a grinding halt. Zolgensma carries a boxed warning on its label stating that the therapy can cause serious liver injury, and patients who already have liver problems face a higher risk.
Another potential limitation stems from the way gene therapy works, by zapping a patient’s cells with a modified virus carrying genetic instructions. But Novartis noted in its recent update that 5 percent (nine of 177) of the children under age 5 screened for Zolgensma had pre-existing defenses that would have destroyed the gene therapy before it could work. They were not eligible for the treatment.
Prior to Zolgensma’s approval, Biogen executives cited the breadth of data on real world patients on Spinraza relative to the Novartis gene therapy and were adamant that Spinraza would remain the standard of care for the disease for “years to come.” In a statement issued on Friday, Biogen took another swipe at Zolgensma, pointing out the FDA’s black box warning and comparative paucity of clinical data. Biogen also called any price comparison between Zolgensma and Spinraza “highly speculative since the long term efficacy of gene therapy is not known.”
“Spinraza continues to be the only treatment available for a broad age range of patients with SMA and remains the only treatment with a well-established safety and durability profile supported by the largest clinical data set with more than 300 patients followed for up to six years,” Biogen said.
Novartis owns Zolgensma through its $8.7 billion buyout of Chicago-based AveXis in 2018. Here’s more on Zolgensma, SMA, and the economic challenges that gene therapy faces.
